Project Summary PCa is the leading cause of cancer-related deaths in American men. Androgen deprivation therapies (ADT) that target and suppress androgen receptor (AR) are the mainstay treatment of advanced prostate cancer. A majority of PCa initially responds well to ADT and is called androgen-dependent prostate cancer (ADPC). However, nearly all PCa treated with ADT become resistant to this treatment over a period of months or years, resulting in castration- resistant prostate cancer (CRPC), a lethal disease. Understanding the molecular events regulating AR transcriptional activities and driving CRPC progression is essential for the development of novel therapeutics to eradicate CRPC. The goal of the applicant is to utilize genomic and bioinformatics approaches to integrate big data to identify the key factors leading to drug resistance in prostate cancer. This will entail providing bioinformatics and integrative genomics analysis to various projects studying genetic and epigenetic regulations of AR cistrome and AR-mediated transcriptional program in the context of CRPC. In addition, Bigger Data will be collected either from public domains or generated internally with various collaborators and will be analyzed through integrative genomics coupled with network modeling to discover the driver events to castration-resistant prostate cancer.